Mortality following recovery from COVID-19 hospitalization: A long-term cohort study

Objectives The long-term mortality risk among patients who survive the acute phase of COVID-19 remains uncertain. As the virus continues to resurge globally and new variants such as NB.1.8.1 and LP.8.1 circulate widely, understanding post-acute mortality risk is increasingly important for clinical management. We therefore investigated the association between COVID-19 hospitalization and all-cause mortality up to 3.5 years in these patients. Methods The study included Clalit Health Services members aged ≥40 years. Hospitalized individuals were those admitted for COVID-19 between March 2020 and December 2021. Uninfected individuals were matched 1:1 by birth year, sex, and Charlson comorbidity score. Follow-up began 30 days after discharge from the last COVID-19 hospitalization and ended on 30 September 2023, or upon all-cause mortality, whichever occurred first. Data were analyzed using Kaplan-Meier curves and multivariable frailty-Cox regression models. We pre-specified age strata (40-64 years and ≥65 years). Results Among 16,445 matched pairs, all-cause mortality was higher in previously hospitalized patients than in uninfected controls (4.91 vs 2.63 per 1000 person-months) with an adjusted hazard ratio of 1.69 (1.57-1.83). Patients aged 40-64 years exhibited a greater relative risk (2.31 [1.79-2.98]) than those aged ≥65 years (1.63 [1.50-1.76]). Cancer, diabetes, congestive heart failure, renal disease, chronic obstructive pulmonary disease, and dementia were all associated with higher post-discharge mortality. Receiving ≥2 doses of COVID-19 vaccine tended to lower mortality risk, particularly in the 40-64 years age group. Conclusions The study demonstrates that survivors of COVID-19 hospitalization face a sustained elevation in all-cause mortality and underscore the need for targeted long-term follow-up and preventive strategies.